Novel BCR-ABL1 Fusion Identified by Targeted Next-Generation Sequencing in a Patient with an atypical Myeloproliferative Neoplasm

By Brent Westra • July 14, 2014

A flow cell used in next-generation sequencing. A complete human genome can be decoded from this slide in a few days.

When standard molecular techniques fail in identifying rare and unusual tumor genetic variants, success is now being found through the use of next-generation sequencing (NGS), as evidenced by a team of researchers at the Mayo Clinic.

The findings, published in Human Pathology, showcased the team using NGS to identify an unusual case of a BRC-ABL1, in which the BRC-ABL1 variation resulted in a junction of the BCR exon 8 to exon 34 of the telemetric CABIN1 gene on 22q11 and fusion with the ABL1 exon a2.

This presented case is instructive, due to initial attempts to characterize the chimeric transcript type that were unsuccessful using standard laboratory molecular diagnostic methods. Utilization of the NGS system erased any ambiguity, and the team further summarized the clinical features and subsequent suboptimal therapeutic responses, in the setting of this particular molecular pathologic abnormality, in the publication.

The report from the team at Mayo Clinic, showcases the value of NGS-based approaches in resolving diagnostically difficult, and/or complex tumor genetic abnormalities when standard molecular techniques fail. Several advantages of using an NGS system include: less input of nucleic acid, optimized amplification, and a potential for larger depth of sequence reads in adequately covered gene regions.

Already, NGS-based diagnostic approaches for targeted re-sequencing of somatic gene mutations are evolving to become part of mainstream clinically validated molecular diagnostic testing in human cancers.

Brent Westra

Brent Westra is a Marketing Segment Manager at Mayo Medical Laboratories. He leads marketing strategies for product management and specialty testing along with new media innovations. Brent has worked at Mayo Clinic since 2011.